Novel discoveries in cancer biology have provided the opportunity to design target-specific anti-cancer agents and fostered advancements in drug development. These discoveries make it possible to design molecules with high selectivity against specific targets in cancer cells. Segota & Bukowski, Cleveland Clinic J. Med., 71(7):551-560 (2004). For example, the success of the Bcr-Abl tyrosine kinase inhibitor imatinib (Gleevec) in the treatment of chronic myeloid leukemia (CML) has inspired great expectation for this targeted approach. Capdeville et al., Nature Reviews, 1:493-502 (2002). Targeted cancer therapy brings with it a critical problem: targets develop escape mutations ultimately leading to drug resistance. For example, it has been reported that mutations have been found to arise in patients that were initially responsive to treatment with Gleevec and who as a result of these mutations are refractory to further treatment with Gleevec. Gone et al., Science, 293:876-880 (2001); Shah et al., Cancer Cell, 2:117-125 (2002); Branford et al., Blood, 99(9):3742-3745 (2002); Deininger et al., Blood, 105(7):2640-263 (2005); Walz et al., Critical Reviews in Oncology/Hematology 57:145-164 (2006); and Burgess et al., The Scientific World JOURNAL, 6:918-930 (2006). Similarly, mutations in epidermal growth factor receptor (EGFR) have been found in non-small cell lung cancer (NSCLC) patients that were reported to make them resistant to the action of therapeutic agents such as gefitinib (Iressa) or erlotinib (Tarceva) that specifically target EGFR. Kobayashi et al., N. Engl. J. Med., 352(8):786-792 (2005). Therefore, the effectiveness of these cancer drugs is significantly limited by the occurrence of escape mutations.
As such, it would be desirable to at least minimize the occurrence of mutants that emerge with the administration of therapeutic and/or prophylactic agents.
Methods for eliciting an immune response are disclosed in for example, Thyphronitis et al., Anticancer Research, Vol. 24:2443-2454 (2004) and Plate et al., Journal of Cell Biology, Vol. 94:1069 (2005). Yeast systems are disclosed in for example, U.S. Pat. No. 5,830,463, Stubbs et al., Nature Med. 5:625-629 (2001); Lu et al., Cancer Research 64:5084-5088 (2004); and Franzusoff, et al., Expert Opin. Bio. Ther. Vol. 5:565-575 (2005).
All references cited herein, including patents, patent applications and publications, are hereby incorporated by reference in their entirety.